Synthesis and structure elucidation of a novel mixed-ligand Cu(II) Schiff base complex and its catalytic performance for the synthesis of 2-amino-4H-pyrans and tetrahydro-4H-chromenes

Article abstract of DOI:10.1016/j.poly.2018.02.013

A novel quinazoline Schiff base ligand, 3-((5-bromo-2-hydroxy-3-methoxybenzylidene)amino)-2-methylquinazolin-4(3H)-one [HL] and its mixed-ligand Cu(II) complex [Cu(L′)(Imi)], [L′] = 2-acetamido-N-(5-bromo-2-oxidobenzylidene) benzohydrazonate, [Imi] = imid

Full text of DOI:10.1016/j.poly.2018.02.013

Accepted Manuscript
Synthesis and structure elucidation of a novel mixed-ligand Cu(II) Schiff base
complex and its catalytic performance for the synthesis of 2-amino-4H-pyrans
and tetrahydro-4H-chromenes
S. Yousef Ebrahimipour, Mehrji Khosravan, Jesus Castro, Fatemeh Khajoee
Nejad, Michal Dusek, Vaclav Eigner
PII:
S0277-5387(18)30080-9
https://doi.org/10.1016/j.poly.2018.02.013
POLY 13048
DOI:
Reference:
Polyhedron
To appear in:
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Accepted Date:
20 November 2017
13 February 2018
Please cite this article as: S.Y. Ebrahimipour, M. Khosravan, J. Castro, F. Khajoee Nejad, M. Dusek, V. Eigner,
Synthesis and structure elucidation of a novel mixed-ligand Cu(II) Schiff base complex and its catalytic performance
for the synthesis of 2-amino-4H-pyrans and tetrahydro-4H-chromenes, Polyhedron (2018), doi: https://doi.org/
10.1016/j.poly.2018.02.013
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Synthesis and structure elucidation of a novel mixed-ligand Cu(II)
Schiff base complex and its catalytic performance for the synthesis
of 2-amino-4H-pyrans and tetrahydro-4H-chromenes
S. Yousef Ebrahimipour*,1,2, Mehrji Khosravan1*, Jesus Castro3, Fatemeh Khajoee
Nejad1, Michal Dusek4, Vaclav Eigner4
1 Department of Chemistry, Faculty of Science, Shahid Bahonar University of Kerman, Kerman,
Iran
2 Department of Chemistry, Payame Noor University (PNU), 19395-4697 Tehran, Iran
3
Departamento de Química Inorgánica, Universidade de Vigo, Facultade de Química, Edificio
de Ciencias Experimentais, 36310 Vigo, Galicia, Spain
4
Institute of Physics, Academy of Sciences of the Czech Republic, Na Slovance 2, 182 21
Prague, Czechia
Corresponding authors:
Dr. S. Yousef Ebrahimipour
Department of Chemistry, Faculty of Science
Shahid Bahonar University of Kerman, 76169-14111, Kerman, Iran
E-mails addresses: Ebrahimipour@uk.ac.ir, Ebrahimipour@ymail.com
Dr Mehrji Khosravan
E-mail address: Mehrjikhosravan44@gmail.com
1

Abstract
A novel quinazoline Schiff base ligand, 3-((5-bromo-2-hydroxy-3-methoxybenzylidene)amino)-
2-methylquinazolin-4(3H)-one [HL] and its mixed-ligand Cu(II) complex [Cu(L’)(Imi)] ,[ L’]=
2-acetamido-N-(5-bromo-2-oxidobenzylidene) benzohydrazonate, [Imi]= imidazole, were
synthesized and characterized by elemental analysis, FT-IR and UV–Vis spectrometry and
conductivity measurements. The structure of [HL] and its Cu(II) complex have been
accomplished by single crystal X-ray diffraction. The Hirshfeld surface analysis has also been
performed to evaluate intermolecular interactions. All experimental results confirmed that in this
complex Cu(II) central atom is coordinated by the donor atoms of deprotonated Schiff base
ligand and nitrogen of imidazole. Furthermore, the catalytic activities of this complex have been
investigated on the electrophilic reaction of malononitrile along with aldehydes, ethyl
acetoacetate and dimedone in ethanol solution in order to obtain 2-amino-4H-pyrans and
tetrahydro-4H-chromenes, respectively
Keywords: Cu(II) schiff base complex, crystal structure, hirshfeld analysis, catalytic activity, 2-
amino-4H-pyrans and tetrahydro-4H-chromenes
Introduction
The synthesize of Schiff base ligands are relatively easy and they can be used in a wide range of
substition reaction [1]. In addition, their properties may be improved or modified by coordination
to various transition metal ions [2]. It has been demonstrated that even a small change in the
ligand structure can considerably change the properties of the corresponding complex. Schiff
2

base complexes containing imine groups are of significant interest [3-4]. For example, the
properties of copper complexes have been investigated and it was found these complexes have
applications in various research areas, including artificial photosynthesis, proteasome inhibitors,
anticancer agents, different catalytic process such as liquid phase oxidation of organic substrates
[5-7]. Accordingly, synthesis of novel copper complexes with improved activities in various
applications have been attracted much attention [8-9].
Multicomponent reactions (MCRs) have recently gained new dimensions in the field of
designing methods to produce elaborate libraries of biologically active compounds [10]. Among
these compounds, 4H-pyrans and 4H-chromenes are heterocyclic compounds with biological and
pharmacological activities including anti-allergic, spasmolytic, diuretic, anti-cancer, and anti-
anaphylactic properties [11].
Due to the mentioned applications of 4H-pyrans and 4H-chromenes, development of suitable
methods for the synthesis of their derivatives have attracted considerable attention [12-15].
Accordingly, the present work was amid to synthesize and characterize an efficient catalyst for
the synthesis of 2-amino-4H-pyrans and tetrahydro-4H-chromenes (Scheme 1) in ethanol as a
green reaction medium. This catalyst was a Cu(II) complex composed of a Schiff base derived
from the reaction between para-boromo salicylaldehyde and 2-methyl-3-amino-quinazoline.
3

Scheme 1: [Cu(L’)(Imi)] catalyzed one pot synthesis of 2-amino-4H-pyrans and tetrahydro-4H-
chromenes in ethanol.
Materials and method
All chemicals and solvents were of analytical reagent grade and were used as received without
further purification. Microanalyses for C, H and N were determined on a Thermo Finnigan Flash
Elemental Analyzer 1112EA. Melting points were measured on an Electrothermal Apparatus-
9100. Infrared spectra were determined by using KBr disk on a FTIR spectrophotometer
Shimadzu model 8400s in the region 400-4000 cm-1. Electronic spectra were recorded in ethanol
solutions on UV-Vis spectrophotometer spectro Scan 80D in 200-800 nm range. Nuclear
Magnetic Resonance spectrum (1H-NMR) for the ligand was recorded on a Bruker AMX 300
spectrometer with tetramethylsilane as an internal standard. Molar conductance measurement
was made by means of a Metrohm 712 Conductometer in EtOH.
Synthesis of 3-((5-bromo-2-hydroxybenzylidene)amino)-2-methylquinazolin-4(3H)-one
[HL]
In a solution of 2-methyl-3-amino-quinazoline (1 mmol, 175 mg) in 10 ml methanol was added
5-bromo-2-hydroxy benzaldehyde (1 mmol, 201 mg). The resulting yellow solution was refluxed
for ca. 45 min. Crystals were obtained by slow evaporation of solution, washed with cold ethanol
and dried in a desiccator over silica gel.
Yield: 84%. M.p.: 121 ˚C. Anal. Calc. for C16H12BrN3O2.22 (361.71 g mol-1): C, 53.13; H, 3.34;
N, 11.62. Found: C, 53.19; H, 3.34; N, 11.68%. FT-IR (KBr, cm-1): ν(OH) 3453, ν(C-Haromatic
)
1
2924-2998, ν(C=O) 1679, ν(C=N) 1608 , ν(C=C ring) 1480, ν(C–O) 1255. H NMR (300 MHz,
4

DMSO-d6, 25 ˚C, ppm) d: δ = 10.88 (s, 1H, OH), 9.14 (s, 1H, CH=N), 6.96 – 8.27 (m, 7H,
aromatic CH). UV/Vis (EtOH) λmax, nm (logε, L mol-1 cm-1): 235 (4.75), 310 (4.34).
Synthesis of Imidazole 2-acetamido-N-(5-bromo-2-oxidobenzylidene) benzohydrazonate
Copper(II) [Cu(L’)(Imi)]
A solution of [HL] (0.1 mmol, 35 mg) and CuNO3.6H2O (0.1 mmol, 30 mg) in methanol (5 ml)
was refluxed for 30 min. Imidazole (0.3 mmol, 0.02 g) was added to the resulting green solution,
which was further refluxed for an additional 10 min. After cooling, the solution was filtered and
left to stand overnight. Reddish crystals suitable for crystallography appeared in the mother
liquor after 1 day.
Yield: 62%. M.p.: 329 ˚C. Molar conductance (10-3 M, DMSO): 11 ohm-1 cm2 mol-1. Anal. Calc.
for C19 H16 Br Cu N5 O3 (505.82 g mol-1): C, 45.12; H, 3.19; N, 13.85. Found: C, 45.10; H, 3.15;
N, 13.90%. FT-IR (KBr, cm-1): ν(NH) 3308, ν(NHimidazole) 3142, ν (C-Haromatic) 2863-3027,
ν(C=O) 1677, ν(C=N) 1588, ν(C=C ring) 1471, ν(C–O) 1251, ν(Cu–O) 522, ν(Cu–N) 460.
UV/Vis (EtOH) λmax, nm (logε, L mol-1 cm-1): 235(4.84), 301(4.43), 395(4.37), 615(3.00)
Crystal structure determination
The diffraction data of [HL] were collected at 120 K on a Gemini Ultra diffractometer (Agilent
Technologies) equipped with an Atlas S2 CCD detector, mirror-collimated CuK radiation (=
1.54184Å) from a sealed X-ray tube, and the CryoJet 5 cooling system. Data collection and data
processing were done with CrysAlis PRO software including absorption correction, which
combined the analytical correction based on the crystal shape and correction by spherical
harmonic functions (the ABSPACK procedure). The structure was solved by program Superflip
5

[16], and refined by program Jana2006 by full matrix least squares on F2. All non-hydrogen
atoms were refined using harmonic refinement. All hydrogen atoms present in the structure
model were discernible in difference Fourier maps and could be refined to reasonable geometry.
According to common practice, H atoms bonded to C were kept in ideal positions with C-H =
0.96 Å while the position of H atom bonded to O2 was refined using an O-H restraint 0.820(1)
Å. In both cases Uiso(H) was set to 1.2 Ueq (C,O). The hydrogen atoms of weakly occupied water
molecule (s.o.f. 22%) could be recognized in the difference electron density maps as faint
maxima but their refinement was unreliable; therefore, they are absent it the structure model.
The diffraction data of [Cu(L’)(Imi)] were collected at 100K in the CACTI (Universidade de
Vigo) at low temperature using a Bruker D8 Venture with a CMOS Photon 100 detector and Mo-
Kα radiation (λ = 0.71073 Å) equipped with a CryoStream 800 system. The software APEX3
[17] was used for collecting frames of data, indexing reflections, and the determination of lattice
parameters, SAINT [17] for integration of intensity of reflections, and SADABS [17] for scaling
and empirical absorption correction. The crystallographic treatment of [Cu(L’)(Imi)]was
performed with the Oscail program [18], using the SHELXT program [19] for structure solution
and SHELXL program [20] for a full matrix least squares refinement on F2. Non-hydrogen
atoms were refined with anisotropic displacement parameters. Hydrogen atoms were included in
idealized positions and refined with isotropic displacement parameters. The Squeeze program
[21] was used to eliminate the reflections caused by a disordered MeOH solvent. Details of
crystal data and structural refinement for both compounds are given in Table S1. PLATON
(version 21116) [22] was used for obtain some geometrical parameters of the cif file and for
perform the Bond Valence Analysis on [Cu(L’)(Imi)].
6

Hirshfeld surface analysis
The Hirshfeld surfaces for HL and for [Cu(L’)(Imi)]were calculated using the Crystal Explorer
v.3.1 program package and the 2D fingerprint was prepared using the same software, by using
reciprocal interactions, that is, both X...Y and Y...X interactions were included in the fingerprints
[23]. For them, two distances de (the distance from the point to the nearest nucleus external to the
surface) and di (the distance to the nearest nucleus internal to the surface) where considered. The
drawn surfaces were determined from the normalized contact distance, dnorm, defined as the sum
of the normalised by the van der Waals radius of the atom involved di and de. [24]. In the input
used for HL, we omitted the weakly occupied (22%) oxygen atom of the water molecule because
we think it cannot affect the packing. On the other hand, in the input used for [Cu(L’)(Imi)]we
added oxygen, carbon and calculated hydroxyl hydrogen of the solvent MeOH. Position of
oxygen and carbon were fixed where the maximum residual densities are, and the position of the
hydrogen atom was calculated by riding methods. . The surfaces were calculated on the dimeric
unit, since we think this is the "molecule" to be considered.
General procedure for the synthesis of 2-amino-4 H -Imirans (1a-6a) and tetrahydro-4H-
chromenes (1b-6b) derivatives
An aromatic aldehydes (1 mmol), malononitrile (1 mmol), ethyl acetoacetate or dimedone (1
mmol) and Schiff base complex as a catalyst (20 mg) were placed in 10 ml round-bottom flask.
The reaction mixture was stirred at 50 °C until the reaction was completed. The progress of the
reaction was monitored by TLC. Upon completion of the reaction, the catalyst was separated by
filtration then washed with acetone and after drying were used in the next reaction without loss
7

of activity. The precipitate was separated by filtration, washed thoroughly with ethyl acetat to
yield the product. Recrystallization was carried out in EtOH/H2O.
Result and discussion
General aspects
There are a few reports about quinazoline-based metal Schiff base complexes. Spectroscopic
data of these reports suggest that the ligand act as a monobasic tridentate or neutral bidentate
complexing agent [25, 26]. Surprisingly, we found that this class of ligands can be hydrolyzed
during the complexation, and so, can act as a dibasic chelating agent [27]. In the present work a
similar mechanism was observed for the coordination of Cu(II) by 3-((5-bromo-2-
hydroxybenzylidene)amino)-2-methylquinazolin-4(3H)-one as illustrated in Fig 1.
Characterization
Infrared Spectroscopic Analysis
In the FTIR spectrum of the ligand, an absorption band was appeared at 3453 cm-1 corresponding
to OH group [28]. However, this peak was not observed in the spectrum of the complex, which is
indicative of the deprotonation of the oxygen atom which is due to the coordination to the metal
ion. Also, HL revealed vibrations of C=O and C=N bands at 1679 and 1608 cm-1, respectively
[29]. In the spectrum of the complex, the band of ʋ(C=N) was observed at 1588 cm-1. So, a red
shift was occurred compared with the ligand spectrum suggesting that the azomethine nitrogen
was coordinated to the metal ion [30]. Additionally, the vibration of C=O in the complex
spectrum was appeared at 1677 cm-1 which is due to hydrolysis of the ligand during the
complexation process. Also, a red shift of 4 cm-1 was observed in ν(C-O) in the complex
8

spectrum in comparision with the free ligand spectrum confirming the coordination of the ligand
to the Cu(II) ion center through the phenolic oxygen atom [31]. In the complex spectrum, the
stretching vibrations of N-H of the amide and imidazole moieties were appeared at 3308 and
3102 cm-1 and those of Cu-O and Cu-N were observed at 522 cm-1 and 460 cm-1, respectively.
Uv-vis absorption Spectral studies
In the Uv-vis spectrum of the ligand, the band appeared at 235 nm is attributed to π-π *
transitions within the aromatic and quinoline rings. The n-π *transition of the C=N group is
observed at 310 nm. In the spectrum of the Cu(II) complex similar features are observed.
Appearance of an absorption peak at 395 nm with the epsilon value of log ε = 4.37 indicates the
coordination of the ligand to the Cu2+ ion. This high epsilon value suggests that the
corresponding band is a result of metal to ligand (MLCT) and ligand to metal (LMCT) charge
transfer transitions. It has been illustrated that SP or distorted SP geometries have a characteristic
band in the wavelength range of 550–660 nm which is related to
while TBP
dxz ,dyz  d
x2 y2
structures show an absorption peak around >800 nm originated from
. Since
dxz ,dx2   dz2
y2
[Cu(L’)(Imi)] shows a band at 652 nm, it can be concluded that the geometry of the Cu(II)
complex is closer to SP [32].
X-ray Crystal structure
Figure 2 displays an ORTEP drawing of the asymmetric unit found in HL, showing the
numbering scheme used. Some bond distances and angles are reported on Table S2_ at the
Supplementary Material. Note that, as was mentioned in the experimental section, a molecule of
water was found with a small occupancy factor (22%), and the hydrogen atoms of this molecule
9

could not be reliably refined. On the other hand, coordinates of the difference Fourier maxima
indicated one hydrogen of water participates in a weak O1w-H…O1 hydrogen bond (Table S3).
Therefore, we have included to the Figure 2 simulated positions of water hydrogen atoms. It is
worth noting that, to the best of our knowledge, there are not any other
(alkylideneamino)quinazolin-4-one compounds described in the literature (CCDC database, CSD
version 5.37 (Feb. 2016 updated) [33]), although several 2,3-dihydroquinazolin-4-one
derivatives [34] were described. HL is therefore planar in clear difference with the
dihydroquinazolinone derivatives, and the distances and angles found in HL are related with the
sp2 character [35] of the carbon atoms in the rings. A detailed description of HL, together with its
supramolecular behaviour and the Hirshfeld surface analysis is provided in the Supplementary
Material.
Description of the Cu(II) complex [Cu(L’)(Imi)]
Figure 3 displays an ORTEP drawing of the asymmetric unit found in [Cu(L’)(Imi)], showing
the numbering scheme used. In the Supplementary Material, Table S4 contains a selection of
bond distances and angles. In the asymmetric unit, the Cu(II) atom is bonded by two oxygen
atoms and one nitrogen atom of the tridentate salicylaldehyde-phenylhydrazonate ligand, and by
another nitrogen atom from neutral imidazole molecule, forming a distorted square-planar
coordination configuration. Noteworthy the presence of another molecule transformed by
symmetry operation 1-x, 2-y, 1-z, which becomes parallel to the original one in such a way that
the oxygen atom of the acetylimide substituent of the ligand is situated at only 2.678(2) Å from
the copper atom. Both are sketched in Figure 4, and this behaviour contrast with the usual one
found in the literature where dimers are constructed by using the phenolato oxygen atom [36,
10

37]. If this bond is considered, the compound is best defined as a dimeric one, where the copper
atoms are square pyramid coordinated ( = 0.13) [38]. A detailed description of [Cu(L’)(Imi)],
together with its supramolecular behaviour and the Hirshfeld surface analysis is provided in the
Supplementary Material.
Hirshfeld surface analysis
Hirshfeld surface analysis allows the visual representation of the interactions in crystal structures
[39]. Several properties of intermolecular interactions can be visualized through mapping onto
this surface: curvedness, shape index, dnorm, etc. In addition, all (di, de) contacts can be expressed
in the form of a two dimensional plot, known as the 2D fingerprint plot [24, 40-41]. Opposite
views of dnorm Hirshfeld surface analysis (see Supplementary Material for definitions) for HL are
shown in Figure 5. In both cases, the neighbour molecule was also sketched to show the O-H···N
interaction. Red spots indicate the intermolecular interactions, and they are found in the
proximity of the phenolic group (hydrogen donor) and in the proximity of the acceptor nitrogen
atom, and they produce the growing of the molecule in the zone axis ( , 0, 1). The parameters of
these hydrogen interactions are set out in Table S5. The plots of 2D fingerprint are included in
the Supplementary Material.
In similar way, opposite views of dnorm Hirshfeld surface analysis for [Cu(L’)(Imi)] are shown in
Figure 6. As was stated in the experimental part, there is a molecule of solvent in the crystal,
probably MeOH, but the quality of the data did not allow to model this molecule. However, since
we were interested in participation of this solvent molecule in intermolecular interactions, a cif
file was generated including those atoms. However, it seems that this molecule does not interact
in a significant manner with the dimeric molecule of [Cu(L’)(Imi)]. Red spots indicate the
11

intermolecular interactions, and they are found, as expected, in the proximity of the free N-H
groups of the imidazole ligand, since this group is forming a classical hydrogen bond with the
oxygen atom of the acetylimide moiety from a neighbour symmetry generated molecule.
Detailed study of these surfaces is provided in the Supplementary Material and the
supramolecular arrangement is related with it. Moreover, plots of 2D fingerprint are included in
the Supplementary material.
Catalytic activity
Initially, in order to optimize the reaction conditions, we used solvents in the three component
reaction of ethylacetoacetate, malononitrile and benzaldehyde in the presence of [Cu(L’)(Imi)]
as a catalyst to investigate the effects of solvent in the preparation of ethyl 6-amino-5-cyano-2-
methyl-4-phenyl-4H-pyran-3-carboxylate (Table 1). In order to optimize the effect of catalyst
loading to this reaction we noted that although the product could be formed with low catalyst
loading (4 mol% of the [Cu(L’)(Imi)]), the best outcome, in terms of yield and the reaction time,
was obtained with 8 mol% of [Cu(L’)(Imi)] (Table 2). In addition the effect of temperature on
this reaction was investigated. It was found that the optimum temperature was 50 °C from the
point of view of yield and reaction time. At higher temperatures, no further improvement on
yield and reaction time was observed. On the other hand, the reaction did not proceed at room
temperature. At 50 °C, the reaction proceeded smoothly and almost complete conversion of the
reagent was observed (Table 1).
Using the optimal solvent and catalyst loading, various 4H pyran derivatives with different
aldehydes were synthesized (Table 3). High yields were obtained; especially when aromatic
12

aldehydes were used containing electron withdrawing groups, much lesser reaction time was
needed in comparison to electrophilic aromatic aldehydes.
In order to synthesize tetrahydro-4H-chromene derivatives, we replaced ethyl acetoacetate in the
reaction with 5,5-dimethyl-1,3-cyclohexanedione. The reaction conditions for the synthesis of 2-
amino-4 H –chromenes were optimized. For this purpose, dimedone, benzaldehye and
malononitrile were used as model substrates. Table 4 and 5 gives the optimization obtained
results. Under the optimal condition, different substrates containing electron donating and
electron releasing groups were investigated. The reactions of all tested substrates were found to
proceed smoothly in a procedure similar to the synthesis of 2-amino-4H-pyrans to give 2-amino-
4 H -chromenes (Table 6). The recyclability of the Cu(II) complex was also evaluated using a
series of three consecutive runs for 1a and 1b using the optimal conditions. No change was
observed in the activity of the catalyst for up to three uses and the yields were as follows: (1a:
95%, 93%, 90%, 1b: 92%, 90%, 89%).
In order to show the efficiency and capability of the present method, our results were compared
with some of the previously reported and published procedures for the synthesis of compound 1a
and 1b. The results, are summarized in Tables S5 and S6, clearly show that the present procedure
exhibits superiority over the other methods in terms of the yield, an easy work-up process,
reaction time and also low temperature.
A plausible mechanism for the formation of 2-amino-4H-pyrans and tetrahydro-4H-chromenes is
depicted in Fig. 7. In the first step of these reactions, 2-arylidenemalononitrile derivatives are
synthesized from Knoevenagel condensation reaction (I). The electrophilic C=C double bond
of 2-arylidenemalononitrile reacts with the methine of cyclic β-dicarbonyl compounds and the
intermediate (II) is formed which tautomerizes to (III). Then, nucleophilic attack of the
13

negatively charged oxygen to the cyano (CN) moiety results in the formation of a new
heterocycle as shown in the intermediate (IV). Finally, tautomerization of (IV) affords products
1a-2g. Herein, the catalytic activity of the Cu(II) complex was established for Knoevenagel
condensation and Michael addition reactions. In these reactions, the central Cu2+ ion acts as a
Lewis acid and coordinates respectively to the oxygen atom of the aldehyde carbonyl and
the nitrogen atom of the cyano moiety. This coordination results in the polarization of the π-
electrons of carbonyl and cyano groups. Finally, these groups are attacked by nucleophiles more
easily (Fig. 7)
Conclusions
A novel tridentate quinazoline-Schiff base ligand [HL] and its mixed-ligand Cu(II) complex
were synthesized and characterized by physico-chemical and spectroscopic methods including
elemental analysis, FT-IR, 1H NMR and UV-Vis spectra data. The structures of compounds were
also determined by single crystal X-ray diffraction. In the title complex, positions around the
central atom being occupied with donor atoms of HL and N donor atom of coordinated
Imidazole. This complex was used as an efficient catalyst in the synthesis of 2-amino-4H-pyrans
and tetrahydro-4H-chromenes. These reactions were carried out in EtOH as a solvent at 50 ˚C. In
comparison to the previous methods high yields, low temperature and reusability of the catalyst
with almost consistent activity are advantages of this procedure that make it more useful process
compare to the existing methods.
Supplementary data
14

Crystallographic data for the free proligand [HL] and [Cu(L’)(Imi)] have been deposited with the
Cambridge Crystallographic Data Centre, CCDC No. 1583955 & 1564391. Copies of this
information may be obtained from the Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ,
UK (fax: +44-1223-336033; email: deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
Acknowledgements
Authors gratefully acknowledge the financial support of the Shahid Bahonar University of
Kerman. The crystallographic part was supported by the project 15-12653S of the Czech Science
Foundation using instruments of the ASTRA lab established within the Operation program
Prague Competitiveness - project CZ.2.16/3.1.00/24510
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17

Figure Captions:
Figure Captions:
Fig. 1. Schematic diagram for hydrolysis processes.
Fig. 2. ORTEP drawing of [HL] (50% probability level). Hydrogen atoms in the water molecule
(22% occupancy factor) were drawn in simulated positions.
Fig. 3. ORTEP [50% probability level] drawing of [Cu(L’)(Imi)].
Fig. 4. Dimer drawn of [Cu(L’)(Imi)].
Fig. 5. Front and back views of dnorm mapped on the Hirshfeld surfaces for [HL].
Fig. 6. Front and back views of dnorm mapped on the Hirshfeld surfaces for [Cu(L’)(Imi)]
Fig. 7. Proposed mechanism for formation of 2-amino-4H-pyrans and tetrahydro-4H-chromenes
using [Cu(L’)(Imi)] as catalyst.
18

Fig. 1.
19

Fig. 2.
20

Fig. 3.
21

Fig. 4.
22

Fig. 5.
23

Fig. 6.
24

Fig. 7.
25

Table 1. Optimization of times and yields in various solvents for the synthesis of Ethyl 6-amino-
5-cyano-2-methyl-4-phenyl-4H-pyran-3-carboxylate (1a)
Solvent
EtOH
Temperature
R.T
Time (min)
Isolated yield %
70
15
15
60
55
75
95
95
80
75
EtOH
50
EtOH
Reflux
Reflux
Reflux
Acetonitrile
Ethyl acetate
26

Table 2. Optimization of the amounts of [Cu(L’)(Imi)] charged as catalyst to the three-
component synthesis ethyl 6-amino-5-cyano-2-methyl-4-phenyl-4H-pyran-3-carboxylate (1a) at
50 °C.
Amount of catalyst
Time (min)
Isolated yield %
(mol%)
0
4
115
40
35
80
95
95
8
15
12
15
27

Table 3. Three-component reaction of ethylacetoacetate (3b), malononitrile (2) and aromatic
aldehydes.
Isolated
Entry
Aldehyde
Time(min)
yield %
95
1a
2a
3a
4a
5a
6a
benzaldehyde
15
18
21
18
17
20
4-chlorobenzaldehyde
4-methoxybenzaldehyde
3-nitrobenzaldehyde
90
89
89
2,4-dichlorobenzaldehyde
4-methylbenzaldehyde
91
88
28

Table 4. Optimization of times and yields in various solvents for the synthesis of 2-amino-4-
phenyl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (1b)
Solvent
EtOH
Temperature
R.T
Time (min)
Isolated yield %
65
20
20
75
60
75
92
92
82
80
EtOH
50
EtOH
Reflux
Reflux
Reflux
Acetonitrile
Ethyl acetate
29